The major emphasis of this project has been the study of the physiology of erythropoietin (EP) in various hematologic disorders in man. Particular emphasis has been placed on the observation that occasional patients with congenital hypoplastic anemia (erythrogenesis imperfecta) have an erythropoietic response to infusions of plasma from normal non-anemic donors. Studies are continuing to determine whether the EP in the serum of these patients is normally active in in vitro systems. Short term marrow cultures from such patients are being compared with marrow from non-anemic subjects as to response to stimulation by erythropoietin in the presence of the patient's serum or in the presence of normal serum. Incident to these studies several significant observations have been made relevant to precision of bioassay methodology and quantitation. EP preparations have been encountered which when quantitated in assay systems measuring different parameters of erythropoietic stimulation have been found to have different expressions of potency in different systems. The implication of these findings, that different kinds of EP molecules exist, possibly stimulating different processes in erythropoiesis, is being in marrow cultures.